We have recently succeeded in the isolation, long-term culture and cloning of capillary endothelial cells. To further study these cells we have developed new assays specifically designed to measure the growth and migration of endothelial cells in vitro. We have found that the controls on growth and migration of capillary endothelial cells are considerably different from those for endothelial cells derived from larger arteries and veins. We propose to employ these capillary endothelial cell cultures as a model system to study the neovascularization (angiogenesis) that is a fundamental component of such pathological states as neoplasia, chronic inflammation, graft versus host immune reactions and delayed hypersensitivity, in addition to being a normal component of wound healing, osteogenesis, luteinization and embryonic development. We will attempt to develop an in vitro assay for angiogenesis based on the ability of an angiogenesis factor to stimulate growth and/or migration of capillary endothelial cells. Similarly, we will develop an assay for angiogenesis inhibitors based on their ability to inhibit growth and/or migration of capillary endothelial cells. We will measure the secreted products of several different cell types such as chondrocytes, mast cells, macrophages, platelets and tumor cells on capillary cell growth and migration and will begin purification of a factor from tumor cells that can promote capillary endothelial cell migration in vitro. Finally, we will investigate the possibility of using in vitro angiogenesis assays as diagnostic tools to detect neoplastic lesions and as tools for the screening of possible chemotherapeutic agents.